Defense Date

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Human Genetics

First Advisor

Amanda Dickinson

Abstract

Abnormalities affecting orofacial development are some of the most common, expensive, and devastating birth defects. Children born with such defects may experience difficulties with eating, breathing, and speech and in addition, these defects often require multiple surgeries to correct them. Therefore, it is critical to understand how the orofacial region develops in order to better treat and prevent these types of birth defects. Xenopus laevis has emerged as a strong model in which to examine orofacial development and was utilized here to investigate the cellular and molecular mechanisms underlying the complex development of the orofacial region. Retinoic acid is one signal involved in orchestrating orofacial development and accomplishes this in part by regulating the nucleosome structure of target genes. The work presented here characterizes the role of an ATP-dependent chromatin remodeler, chromodomain helicase DNA binding protein 1 (Chd1), in orofacial development in X. laevis. The spatial expression of Chd1 supports its role in orofacial development and reduced expression of Chd1 resulted in abnormal facial development. Closer examination of Chd1 morphant embryos revealed that Chd1 is required for the expression of important neural crest and cartilage genes that are necessary for proper development of the face. In addition, there was an increase in apoptosis in regions consistent with migrating neural crest and neural crest derived structures. As a consequence, many of the facial cartilages do not form properly in morphant embryos resulting in a smaller face. Further, this work presents evidence that Chd1 may cooperate with retinoic acid to regulate orofacial development in X. laevis.

Rights

© Brent Wyatt

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-3-2018

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